Abstract

Molecular alterations as a result of exposure to low doses of high linear energy transfer (LET) radiation can have deleterious short- and long-term consequences on crew members embarking on long distance space missions. Oxygen ions (¹⁶O) are among the high LET charged particles that make up the radiation environment inside a vehicle in deep space. We used mass spectrometry-based metabolomics to characterize urinary metabolic profiles of male C57BL/6J mice exposed to a single dose of 0.1, 0.25 and 1.0 Gy of ¹⁶O (600 MeV/n) at 10 and 30 days post-exposure to delineate radiation-induced metabolic alterations. We recognized a significant down regulation of several classes of metabolites including cresols and tryptophan metabolites, ketoacids and their derivatives upon exposure to 0.1 and 0.25 Gy after 10 days. While some of these changes reverted to near normal by 30 days, some metabolites including p-Cresol sulfate, oxalosuccinic acid, and indoxylsulfate remained dysregulated at 30 days, suggesting long term prognosis on metabolism. Pathway analysis revealed a long-term dysregulation in multiple pathways including tryptophan and porphyrin metabolism. These results suggest that low doses of high-LET charged particle irradiation may have long-term implications on metabolic imbalance.

摘要

暴露于低剂量高线性能量转移 (LET) 辐射导致的分子改变可能对执行长距离太空任务的机组人员产生有害的短期和长期后果。氧离子 ( ¹⁶ O) 是构成深空飞行器内部辐射环境的高 LET 带电粒子之一。我们使用基于质谱的代谢组学来表征暴露于单剂量 0.1、0.25 和 1.0 Gy ^{16的雄性 C57BL/6J 小鼠的尿液代谢特征}O (600 MeV/n) 在暴露后 10 天和 30 天，以描绘辐射引起的代谢改变。我们认识到在 10 天后暴露于 0.1 和 0.25 Gy 时，几类代谢物的显着下调，包括甲酚和色氨酸代谢物、酮酸及其衍生物。虽然其中一些变化在 30 天时恢复到接近正常水平，但包括对甲酚硫酸盐、草酰琥珀酸和吲哚硫酸盐在内的一些代谢物在 30 天时仍然失调，这表明代谢有长期预后。通路分析揭示了多种通路的长期失调，包括色氨酸和卟啉代谢。这些结果表明，低剂量的高 LET 带电粒子辐射可能对代谢失衡具有长期影响。